Impact: Prevention of Clostridium difficile is a priority of the VA, and implementation of a C. difficile prevention bundle, akin to an already established methicillin-resistant Staphylococcus aureus (MRSA) bundle, has recently been rolled out nationally. However, our ability to devise and implement strategies for containment of C. difficile is hampered by a limited understanding of factors influencing acquisition, spread, and prevention of C. difficile. Immediate benefits of achieving the objectives of this proposal will be generation of important data regarding barriers and facilitators of implementation using a systems engineering approach. Our study will produce data, methods, and tools that have widespread relevance and portability, with the potential to reduce healthcare-associated infections (HAIs) including but not limited to C. difficile infection. Background: C. difficile is the major infectious cause of nosocomial diarrhea, causing as many as 25% of cases of nosocomial diarrhea. C. difficile infection (CDI) is increasing in incidence and severity, affects 500,000 Americans each year, causes 20,000 deaths annually, and imposes a significant financial burden on healthcare institutions - $1.1 billion annually in the U.S. Preventing CDI is essential; thus, the Veterans Affairs Multidrug Resistant Organism (MDRO) Program Office has recently mandated a national bundle for prevention of CDI at VA facilities. The bundle includes appropriate diagnostic testing, optimization of hand hygiene compliance by monitoring, contact isolation for CDI, and environmental cleaning of rooms of patients with CDI. However, it does not address optimum implementation strategies to ensure successful application of these interventions. Nor does it prescribe how these measures may be undertaken. Implementing and adhering to these recommended measures varies considerably across institutions. Objectives: We hypothesize that a number of work system barriers may pose challenges to successful acceptance, adoption, and implementation of the CDI bundle. Our objective is to assess work system barriers and facilitators to bundle implementation using a mixed-methods approach. We will undertake direct observations of practices relevant to CDI prevention; conduct focus groups of healthcare workers (HCWs); and use vignettes to examine HCW perceptions, attitudes, & decision-making about CDI prevention. Methods: We will use the innovative Systems Engineering Initiative for Patient Safety (SEIPS) model of work system and patient safety as the study framework. This model, as well as general literature on guideline implementation, will guide focus group questions. Three focus groups will be conducted. Participants will include nurses, physicians, and environmental services. Each session will include 4-5 open-ended questions (covering 60-90 min). We will design paper case vignettes depicting patients with or at risk for CDI, and we will ask physicians, nurses, and environmental services staff about relevant infection control practices for CDI prevention. Healthcare workers will be asked whether they would undertake diagnostic testing for CDI and whether they would prescribe empiric treatment, isolation, or reduce concomitant antibiotics. Vignette data will be analyzed using the method of judgment analysis. Finally, we will conduct direct observations of HCWs based on the SEIPS model. We will observe patient rooms, individuals, tasks, and organization to better understand the overall work system that surrounds the process of care for CDI patients. This is among the first research studies to systematically examine barriers and facilitators of implemen- tation of a prevention bundle for CDI, which is a major HAI. Our project is innovative in that it will employ the SEIPS framework to undertake a complete work systems analysis for CDI prevention; use a number of complementary approaches to data collection; and consider not just HCWs involved in direct patient care, but also ancillary staff who are critical to successful CDI prevention. Our study methods and approach may be widely used not just for CDI but also other HAIs, and will add to the fields of patient safety and infection control.